Targeted Therapy for Solid Tumors

Recruiting at 471 trial locations

Overseen by James M Ford

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Solid tumors, Advanced stage, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This ComboMATCH patient screening trial is the gateway to a coordinated set of clinical trials to study cancer treatment directed by genetic testing. Patients with solid tumors that have spread to nearby tissue or lymph nodes (locally advanced) or have spread to other places in the body (advanced) and have progressed on at least one line of standard systemic therapy or have no standard treatment that has been shown to prolong overall survival may be candidates for these trials. Genetic tests look at the unique genetic material (genes) of patients' tumor cells. Patients with some genetic changes or abnormalities (mutations) may benefit from treatment that targets that particular genetic mutation. ComboMATCH is designed to match patients to a treatment that may work to control their tumor and may help doctors plan better treatment for patients with locally advanced or advanced solid tumors.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Binimetinib for treating solid tumors?

Research shows that Binimetinib, when used with other drugs, has shown effectiveness in treating advanced solid tumors, especially in cases with specific genetic mutations like BRAF and NRAS in melanoma. It has also been studied in combination with other treatments for colorectal cancer and non-small cell lung cancer, showing potential benefits. ^{1 2 3 4 5}

Is binimetinib safe for humans?

Binimetinib has been studied in various clinical trials and has shown an acceptable safety profile in patients with certain types of cancer, such as melanoma and non-small-cell lung cancer. It has been tested alone and in combination with other drugs, and the studies have helped determine safe dosage levels for humans. ^{1 2 3 6 7}

What makes the drug combination of Binimetinib, Fulvestrant, Ipatasertib, Leucovorin, Nilotinib, Olaparib, Palbociclib, Selumetinib, and Sotorasib unique for treating solid tumors?

This drug combination is unique because it targets specific genetic and immunological changes in solid tumors, potentially improving survival by using multiple agents that affect different pathways. This approach is part of a new wave of targeted therapies that aim to personalize treatment based on the tumor's characteristics, offering hope for better outcomes in cancers that have limited treatment options. ^{4 8 9 10 11}

Research Team

James M Ford

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for adults with advanced solid tumors that have spread and are not responding to standard treatments or lack treatment options proven to extend life. Participants need available tumor tissue samples, must be in fair health (ECOG 0-2), and willing to undergo genetic testing of their tumors. It's not suitable for those who've had a good response to recent therapies.

Inclusion Criteria

My condition worsened after at least one standard treatment.

I am mostly active and can care for myself.

You need to have samples of your tumor preserved in a specific way.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Registration

Patients undergo tumor mutational screening of previously-collected tumor samples for specific, pre-defined mutations, amplifications, or translocations of interest via tumor sequencing.

2-4 weeks

1 visit (in-person)

Treatment

Patients with mutations targeted to investigational combination therapies are assigned to 1 of 20 treatment subprotocols. Treatment includes various drug administrations and monitoring procedures.

28 days per cycle, up to 5 years

Multiple visits per cycle (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up includes CT or MRI scans and blood sample collections.

Up to 3 years

Every 3 months for 2 years, then every 6 months for 1 year

Treatment Details

Interventions

• Binimetinib (Targeted Therapy)
• Biopsy (Procedure)
• Biospecimen Collection (Procedure)
• Bone Marrow Aspiration (Procedure)
• Bone Scan (Procedure)
• Computed Tomography (Procedure)
• Echocardiography (Procedure)
• Fluorouracil (Chemotherapy)
• Fulvestrant (Hormone Therapy)
• Ipatasertib (Targeted Therapy)
• Leucovorin (Chemotherapy)
• Magnetic Resonance Imaging (Procedure)
• Multigated Acquisition Scan (Procedure)
• Mutation Carrier Screening (Procedure)
• Nilotinib Hydrochloride Monohydrate (Targeted Therapy)
• Olaparib (Targeted Therapy)
• Oxaliplatin (Chemotherapy)
• Paclitaxel (Chemotherapy)
• Palbociclib (Targeted Therapy)
• Positron Emission Tomography (Procedure)
• Selumetinib Sulfate (Targeted Therapy)
• Sotorasib (Targeted Therapy)

Trial Overview The ComboMATCH trial tests targeted therapies based on genetic mutations in patients' tumors. Various drugs like Oxaliplatin, Ipatasertib, and Olaparib are matched with specific genetic changes identified through testing. The study aims to control the tumor growth by personalizing treatment plans.

Participant Groups

Group I: EAY191-S3 (activating AKT mutation) Experimental Treatment 6 Interventions

Patients receive paclitaxel IV on days 1, 8, and 15 and ipatasertib PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 35 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo a CT or MRI and blood collection throughout the trial. Patients also undergo a tumor biopsy during screening and optionally during follow-up.

Group II: EAY191-N5 Arm II (neratinib maleate,palbociclib) Experimental Treatment 8 Interventions

Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 and palbociclib PO QD on days 1-21 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

Group III: EAY191-N4 Arm I (RAS pathway mutations) Experimental Treatment 9 Interventions

Patients receive selumetinib PO and olaparib PO on study. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

Group IV: EAY191-N2 Cohort II (NF1 mutations) Experimental Treatment 9 Interventions

Patients receive fulvestrant IM on day 1 of each cycle and binimetinib PO BID on days 15-28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo a CT, MRI, or bone scan, ECHO or MUGA and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group V: EAY191-N2 Cohort I (Arm II) (NF1 mutations) Experimental Treatment 8 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who progress on fulvestrant alone may migrate to cohort II if they meet the migration eligibility criteria. Patients not willing to migrate to cohort II will have further therapy at the investigator's discretion. Patients undergo a CT, MRI, or bone scan and tumor biopsy, as well as ECHO or MUGA and possible blood sample collection during screening and on study.

Group VI: EAY191-N2 Cohort I (Arm I) (NF1 mutations) Experimental Treatment 9 Interventions

Patients receive fulvestrant IM on day 1 and day 15 of cycle 1 and day 1 of subsequent cycles and binimetinib PO BID on days 15 to 28 of cycle 1 and day 1 through 28 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a CT, MRI, or bone scan, ECHO or MUGA, and tumor biopsy, as well as possible blood sample collection during screening and on study.

Group VII: EAY191-E5 Cohort II (sotorasib) Experimental Treatment 6 Interventions

Patients receive combination therapy as in EAY191-E5 Arm A.

Group VIII: EAY191-E5 Cohort I Arm A (sotorasib, panitumumab) Experimental Treatment 6 Interventions

Patients receive sotorasib PO QD on days 1-28 and panitumumab IV on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Group IX: EAY191-E4 (taxane therapy) Experimental Treatment 6 Interventions

Patients receive nilotinib hydrochloride monohydrate PO BID on days 1-28 and paclitaxel IV over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo CT or MRI during screening or cycle 1 day 1, every 2 cycles for 1 year, every 3 cycles for patients on study for more than 1 year, and every 4 cycles for patients on study for more than 3 years and may also undergo CT or MRI during follow-up every 3 months for 2 years and then every 6 months for 1 year if clinically indicated. Patients also undergo collection of blood samples at baseline, cycle 2 day 1, and optionally at progression as well as tumor biopsy at baseline and optionally at progression.

Group X: EAY191-A6 Arm II (RAS/RAF/MEK/ERK mutations) Experimental Treatment 11 Interventions

Patients receive binimetinib PO, leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or an FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated

Group XI: EAY191-A6 Arm I (RAS/RAF/MEK/ERK mutations) Experimental Treatment 11 Interventions

Patients receive leucovorin IV, oxaliplatin IV, and fluorouracil IV on study. Patients undergo ECHO and MUGA during screening and on study, a CT with contrast, MRI, or a FDG-PET during screening, collection of blood during screening and on study, and a biopsy during screening. Patients may also undergo brain MRI or CT during screening and on study, bone scans on study, and biopsy on study if clinically indicated.

Group XII: EAY191-A3 Monotherapy Cohort 1 (binimetinib) Experimental Treatment 6 Interventions

Patients receive binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

Group XIII: EAY191-A3 Combo Cohorts 1, 2, 3, 4 (palbociclib, binimetinib) Experimental Treatment 6 Interventions

Patients receive palbociclib PO and binimetinib PO throughout the trial. Patients may also undergo biopsy at screening and undergo MRI, CT, bone scan, and collection of blood samples during screening, on study, and/or during follow up.

Group XIV: EAY191-A2 (Cohort 3, Arm D) Experimental Treatment 7 Interventions

Cohort 3, Arm D: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XV: EAY191-A2 (Cohort 2, Arm C) Experimental Treatment 7 Interventions

Cohort 2, Arm C: Patients receive olaparib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients experiencing disease progression have the option to migrate to Cohort 3, Arm D. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVI: EAY191-A2 (Cohort 2, Arm B) Experimental Treatment 8 Interventions

Cohort 2, Arm B: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVII: EAY191-A2 (Cohort 1, Arm A) Experimental Treatment 8 Interventions

Cohort 1, Arm A: Patients receive olaparib PO BID and alpelisib PO daily on days 1-28 of each cycle. Cycles repeat every 28 days for up to 5 years in the absence of disease progression, unacceptable toxicity, or bone marrow findings consistent with MDS or AML. Patients also undergo MRI, CT, and/or PET scans throughout the trial and a biopsy prior to treatment start. Patients may also undergo bone scans on study as clinically indicated. Patients have the option to also undergo blood collection throughout the trial and a second biopsy at time of disease progression.

Group XVIII: EAY191-N5 Arm I (neratinib maleate) Active Control 7 Interventions

Patients receive neratinib maleate PO QD on days 1-14 of cycle 0 in the absence of disease progression or unacceptable toxicity. Patients then receive neratinib maleate PO QD on days 1-28 of each subsequent cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who experience progression may crossover to Arm II. Patients undergo ECHO or MUGA during screening and on study, and CT or MRI and collection of blood samples throughout the trial. Patients may also undergo tumor biopsy during screening and on study.

Group XIX: EAY191-E5 Cohort I Arm B (sotorasib) Active Control 5 Interventions

Patients receive sotorasib PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to cohort II. Patients also undergo collection of blood samples, biopsy, and CT or MRI on study.

Group XX: EAY191-N4 Arm II (RAS pathway mutations) Active Control 8 Interventions

Patients receive selumetinib PO on study. Patients who experience progression may elect to cross over to Arm I provided they have not had dose limiting toxicities to monotherapy selumetinib. Patients also undergo a tumor biopsy and blood collection during screening and on study, as well as ECHO or MUGA and CT scans throughout the trial. Patients may undergo bone marrow aspiration or biopsy as clinically indicated.

Binimetinib is already approved in Canada, Japan for the following indications:

Approved in Canada as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600E or V600K mutation

Approved in Japan as Mektovi for:

• Unresectable or metastatic melanoma with a BRAF V600 mutation

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

Binimetinib, an uncompetitive inhibitor of MEK1/2, has shown significant efficacy in treating metastatic melanoma, particularly in combination with encorafenib, resulting in a progression-free survival (PFS) of 14.9 months compared to 7.3 months with vemurafenib alone in Phase 3 trials.

While binimetinib has a tolerable safety profile, there is currently no long-term data on durable responses or overall survival benefits compared to other treatments, highlighting the need for individualized treatment plans for patients with BRAF-mutated metastatic melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The discovery and development of binimetinib for the treatment of melanoma. Tran, B., Cohen, MS.[2021]

In a phase 1 study involving 93 patients with advanced solid tumors, binimetinib was found to have a maximum tolerated dose (MTD) of 60 mg twice daily, but the recommended dose for further studies was adjusted to 45 mg due to ocular toxicity.

Binimetinib showed a manageable safety profile with common side effects including rash and nausea, and demonstrated preliminary anti-tumor activity with three patients with biliary cancer achieving objective responses, indicating potential for further investigation in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. Bendell, JC., Javle, M., Bekaii-Saab, TS., et al.[2022]

In a phase Ib study involving 89 patients with advanced solid tumors, the combination of binimetinib (a MEK inhibitor) and buparlisib (a PI3K inhibitor) showed some efficacy, particularly in RAS/BRAF-mutant ovarian cancer, where 12% of patients achieved a partial response.

However, the treatment was associated with significant toxicities, leading to a lower than expected dose intensity, suggesting that alternative dosing strategies, like pulsatile dosing, may be necessary to improve safety and tolerability in future trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. Bardia, A., Gounder, M., Rodon, J., et al.[2023]

In a phase I study involving 26 patients with metastatic colorectal cancer, the combination of oral binimetinib and FOLFOX was found to have a maximum tolerated dose of 45 mg taken twice daily, with no dose-limiting toxicities observed.

The treatment showed some antitumor activity, with 9 out of 13 patients on continuous dosing achieving stable disease after 2 months, and a median progression-free survival of 3.5 months, indicating potential efficacy in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy. Cho, M., Gong, J., Frankel, P., et al.[2022]

The phase I study found that the MEK inhibitor binimetinib, when combined with carboplatin and pemetrexed, has a recommended phase II dose of 30 mg BID and shows manageable toxicity, with 61.5% of patients experiencing grade 3/4 adverse events.

The treatment demonstrated promising efficacy, with a 50% objective response rate and an 83.3% disease control rate in patients with advanced non-squamous NSCLC, particularly in those with KRAS/NRAS mutations, who had a higher response rate of 62.5%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. Fung, AS., Graham, DM., Chen, EX., et al.[2021]

In a phase II study involving 98 patients with BRAFV600E-mutant metastatic non-small-cell lung cancer (NSCLC), the combination of encorafenib and binimetinib achieved a confirmed objective response rate of 75% in treatment-naïve patients and 46% in previously treated patients, indicating significant efficacy.

The treatment was generally well-tolerated, with common side effects including nausea (50%) and diarrhea (43%), but it also led to dose reductions in 24% of patients and one serious adverse event of intracranial hemorrhage, highlighting the importance of monitoring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. Riely, GJ., Smit, EF., Ahn, MJ., et al.[2023]

In a study involving six patients with EGFR-mutated lung adenocarcinoma, the combination of osimertinib and ramucirumab was found to be generally safe, with only one case of dose-limiting toxicity (grade 3 appetite loss) and no other severe adverse events reported.

Five out of six patients showed a partial response to the treatment, with a median progression-free survival of 9.2 months for those with the EGFR T790M mutation, suggesting promising efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. Akamatsu, H., Ozawa, Y., Oyanagi, J., et al.[2023]

A 67-year-old male patient with heavily pre-treated metastatic non-small cell lung carcinoma showed a major disease response after six months of treatment with sunitinib, a multitargeted tyrosine kinase inhibitor.

Sunitinib demonstrated a good safety profile with no high-grade toxicities, making it a promising option for patients with limited treatment choices in advanced lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient. Tassi, R., Muto, A., Rangan, S., et al.[2018]

Targeted and immunological therapies have significantly improved survival rates in patients with solid tumors, demonstrating the effectiveness of treatments that focus on specific genetic and immunological changes in tumors.

Current clinical trials are exploring the optimal timing and sequencing of these therapies, which include various approved agents for cancers like prostate, breast, lung, and melanoma, indicating a shift towards more personalized cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. Grünwald, V., Rickmann, M.[2021]

For patients with relapsed or progressive non-small cell lung cancer (NSCLC), treatment options are limited after conventional chemotherapy, with only erlotinib and crizotinib approved as third-line therapies in the U.S.

The review emphasizes the importance of identifying molecular characteristics of tumors to improve the effectiveness of targeted therapies, suggesting that agents affecting multiple pathways may offer significant clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). Langer, CJ., Mok, T., Postmus, PE.[2022]

In a study involving patients with advanced solid tumors, the combination of sunitinib at 37.5 mg per day and irinotecan showed some antitumor activity, with 3 out of 10 patients responding, but it also caused significant side effects like neutropenia and sepsis.

The lower dose of sunitinib at 25 mg per day was better tolerated with no dose-limiting toxicities, but it did not demonstrate any antitumor activity, leading to the conclusion that this combination therapy will not be further investigated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. Boven, E., Massard, C., Armand, JP., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

The discovery and development of binimetinib for the treatment of melanoma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A phase 1 dose-escalation and expansion study of binimetinib (MEK162), a potent and selective oral MEK1/2 inhibitor. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Combination Therapy with MEK Inhibitor Binimetinib and Phosphatidylinositol 3-Kinase Inhibitor Buparlisib in Patients with Advanced Solid Tumors with RAS/RAF Alterations. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A phase I clinical trial of binimetinib in combination with FOLFOX in patients with advanced metastatic colorectal cancer who failed prior standard therapy. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

A phase I study of binimetinib (MEK 162), a MEK inhibitor, plus carboplatin and pemetrexed chemotherapy in non-squamous non-small cell lung cancer. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non-Small-Cell Lung Cancer. [2023]

7. Greece pubmed.ncbi.nlm.nih.gov

Phase Ib Study of Osimertinib Plus Ramucirumab in Japanese Lung Cancer Patients With EGFR Mutation. [2023]

8. Greece pubmed.ncbi.nlm.nih.gov

Response and safety of sunitinib in a heavily pre-treated metastatic non-small cell lung carcinoma patient. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of solid tumors. New hopes and frustrations]. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Targeted agents in the third-/fourth-line treatment of patients with advanced (stage III/IV) non-small cell lung cancer (NSCLC). [2022]

11. England pubmed.ncbi.nlm.nih.gov

A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours. [2021]